A new therapeutic method focusing on inhibition of PD-L1 against Candida albicans

A group from Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, China, etc. has reported about a negative role of PD-L1 expression on the host immune response, which inhibits neutrophil migration from the bone marrow into the infected sites for favoring immune escape of fungi infections.

Candida albicans is both a commensal and opportunistic fungal pathogen of humans. During systemic infection, C. albicans enters the bloodstream and disseminates throughout the body, causing the disease known as invasive candidiasis. The successful clearance of C. albicans from the host mainly relies on neutrophils by releasing proinflammatory cytokines, producing reactive oxygen species and anti-microbial peptides, and forming neutrophil extracellular traps.

PD-L1 is found to be expressed on the plasma membrane of immune cells, including neutrophils, B cells, dendritic cells, and macrophages. During C. albicans infection, β-glucans exposed on the cell wall of C. albicans play an important role in modulation of the host response. The C-type lectin receptor Dectin-1 (encoded by Clec7a gene) is the most important neutrophil pattern recognition receptor for the recognition of β-glucans.

In this study, it was demonstrated that activation of Dectin-1 by fungal β-glucans induced PD-L1 expression in murine and human neutrophils, and the upregulated PD-L1 inhibits neutrophil migration from the bone marrow into the infected sites through regulating their autocrine secretion of chemokines CXCL1 and CXCL2. This finding provides new insights that PD-L1 would function as a potent therapeutic target of neutrophil-based immunotherapy against fungal infections through regulating neutrophil release from the bone marrow. That is, either PD-L1 blockade or pharmacological inhibition of PD-L1 expression significantly increased neutrophil release from bone marrow to enhance host antifungal immunity.